271 research outputs found

    Examination of Annular-Electrode Spark Discharges in Flowing Oxygen - An Overview

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    A parametric study of annular spark gaps, pressures, and spark discharges in flowing oxygen gas was performed with a Champion spark exciter. The range of the pressure-distance product for the experiment is from approximately 50 torr-cm to 2500 torr-cm. Measurements of breakdown voltage qualitatively trend with Paschen's curve. Spark duration remained constant until the pressure-distance product exceeded 200 torr-cm, and then steadily increased. The mean spark energy increases linearly with the pressure-distance on a log-log plot indicating that a definite power relationship exists. The distribution of sparks at low energies and low pressures is not Gaussian and has no dominant peaks. Moderate and high spark energies are bimodal, with the dominant mode near 80 mJ. As pressure increases, dominant and secondary modes approach the same probability

    Examination of Annular-Electrode Spark Discharges in Flowing Oxygen Experimental Nuances

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    Microsecond sparks and the resulting plume of hot gas/plasma were examined against a parametric pressure-distance matrix. Schlieren imaging is used to capture the spatial and temporal location of spark discharge exhaust for two milliseconds. Low pressure and larger gap widths created the largest size and intensity signal for the spark-affected plumes. Experimental exit-plume velocities trend well with analytic predictions using a mean pressure between the chamber and atmospheric conditions. Due to the quadratic relation of the annulus area and gap width, larger gap width velocities are more accurately represented by analytic predictions using atmospheric pressure as the larger exit area restricts the flow less. The same pressure adjustment, when applied to breakdown voltages, improves data alignment with Paschens Curve

    Development of Ionic Liquid Monopropellants for In-Space Propulsion

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    A family of new, low toxicity, high energy monopropellants is currently being evaluated at NASA Marshall Space Flight Center for in-space rocket engine applications such as reaction control engines. These ionic liquid monopropellants, developed in recent years by the Air Force Research Laboratory, could offer system simplification, less in-flight thermal management, and reduced handling precautions, while increasing propellant energy density as compared to traditional storable in-space propellants such as hydrazine and nitrogen tetroxide. However, challenges exist in identifying ignition schemes for these ionic liquid monopropellants, which are known to burn at much hotter combustion temperatures compared to traditional monopropellants such as hydrazine. The high temperature combustion of these new monopropellants make the use of typical ignition catalyst beds prohibitive since the catalyst cannot withstand the elevated temperatures. Current research efforts are focused on monopropellant ignition and burn rate characterization, parameters that are important in the fundamental understanding of the monopropellant behavior and the eventual design of a thruster. Laboratory studies will be conducted using alternative ignition techniques such as laser-induced spark ignition and hot wire ignition. Ignition delay, defined as the time between the introduction of the ignition source and the first sign of light emission from a developing flame kernel, will be measured using Schlieren visualization. An optically-accessible liquid monopropellant burner, shown schematically in Figure 1 and similar in design to apparatuses used by other researchers to study solid and liquid monopropellants, will be used to determine propellant burn rate as a function of pressure and initial propellant temperature. The burn rate will be measured via high speed imaging through the chamber s windows

    Arc-Heater Facility for Hot Hydrogen Exposure of Nuclear Thermal Rocket Materials

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    A hyper-thermal environment simulator is described for hot hydrogen exposure of nuclear thermal rocket material specimens and component development. This newly established testing capability uses a high-power, multi-gas, segmented arc-heater to produce high-temperature pressurized hydrogen flows representative of practical reactor core environments and is intended to serve. as a low cost test facility for the purpose of investigating and characterizing candidate fueUstructura1 materials and improving associated processing/fabrication techniques. Design and development efforts are thoroughly summarized, including thermal hydraulics analysis and simulation results, and facility operating characteristics are reported, as determined from a series of baseline performance mapping tests

    A Potential Supernova Remnant/X-ray Binary Association in M31

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    The well-studied X-ray/Optical/Radio supernova remnant DDB 1-15 (CXOM31 J004327.8+411829; r3-63) in M31 has been investigated with archival XMM-Newton and Chandra observations. The timing data from XMM-Newton reveals a power density spectrum (PDS) characteristic of accreting compact objects in X-ray binaries (XRBs). The PDS shows features typical of Roche lobe overflow accretion, hinting that the XRB is low-mass. The Chandra observations resolve the SNR into a shell and show a variable count rate at the 94% confidence level in the northwest quadrant. Together, these XMM-Newton and Chandra data suggest that there is an XRB in the SNR r3-63 and that the XRB is located in the northwestern portion of the SNR. The currently-available X-ray and optical data show no evidence that the XRB is high-mass. If the XRB is low-mass, r3-63 would be the first SNR found to contain a low-mass X-ray binary.Comment: 30 pages, 3 tables, 11 figures, accepted for publication in Ap

    ÎČ1 integrin mediates an alternative survival pathway in breast cancer cells resistant to lapatinib

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    Abstract Introduction The overexpression of human epidermal growth factor receptor (HER)-2 in 20% of human breast cancers and its association with aggressive growth has led to widespread use of HER2-targeted therapies, such as trastuzumab (T) and lapatinib (L). Despite the success of these drugs, their efficacy is limited in patients whose tumors demonstrate de novo or acquired resistance to treatment. The ÎČ1 integrin resides on the membrane of the breast cancer cell, activating several elements of breast tumor progression including proliferation and survival. Methods We developed a panel of HER2-overexpressing cell lines resistant to L, T, and the potent LT combination through long-term exposure and validated these models in 3D culture. Parental and L/T/LT-resistant cells were subject to HER2 and ÎČ1 integrin inhibitors in 3D and monitored for 12 days, followed by quantification of colony number. Parallel experiments were conducted where cells were either stained for Ki-67 and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) or harvested for protein and analyzed by immunoblot. Results were subjected to statistical testing using analysis of variance and linear contrasts, followed by adjustment with the Sidak method. Results Using multiple cell lines including BT474 and HCC1954, we reveal that in L and LT resistance, where phosphorylation of EGFR/HER1, HER2, and HER3 are strongly inhibited, kinases downstream of ÎČ1 integrin--including focal adhesion kinase (FAK) and Src--are up-regulated. Blockade of ÎČ1 by the antibody AIIB2 abrogates this up-regulation and functionally achieves significant growth inhibition of L and LT resistant cells in 3D, without dramatically affecting the parental cells. SiRNA against ÎČ1 as well as pharmacologic inhibition of FAK achieve the same growth inhibitory effect. In contrast, trastuzumab-resistant cells, which retain high levels of phosphorylated EGFR/HER1, HER2, and HER3, are only modestly growth-inhibited by AIIB2. Conclusions Our data suggest that HER2 activity, which is suppressed in resistance involving L but not T alone, dictates whether ÎČ1 mediates an alternative pathway driving resistance. Our findings justify clinical studies investigating the inhibition of ÎČ1 or its downstream signaling moieties as strategies to overcome acquired L and LT resistance

    Effective bridging therapy can improve CD19 CAR-T outcomes while maintaining safety in patients with large B-cell lymphoma

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    The impact of bridging therapy (BT) on CD19-directed chimeric antigen receptor T-cell (CD19CAR-T) outcomes in large B-cell lymphoma (LBCL) is poorly characterised. Current practice is guided by physician preference rather than established evidence. Identification of effective BT modalities and factors predictive of response could improve CAR-T intention to treat and clinical outcomes. We assessed BT modality and response in 375 adult LBCL patients in relation to outcomes following axicabtagene ciloleucel (Axi-cel) or tisagenlecleucel (Tisa-cel). The majority of patients received BT with chemotherapy (57%) or radiotherapy (17%). We observed that BT was safe for patients, with minimal morbidity/mortality. We showed that complete or partial response to BT conferred a 42% reduction in disease progression and death following CD19CAR-T therapy. Multivariate analysis identified several factors associated with likelihood of response to BT, including response to last line therapy, the absence of bulky disease, and the use of Polatuzumab-containing chemotherapy regimens. Our data suggested that complete/partial response to BT may be more important for Tisa-cel than Axi-cel, as all Tisa-cel patients with less than partial response to BT experienced frank relapse within 12 months of CD19CAR-T infusion. In summary, BT in LBCL should be carefully planned towards optimal response and disease debulking, to improve CD19CAR-T patient outcomes. Polatuzumab-containing regimens should be strongly considered for all suitable patients, and failure to achieve complete/partial response to BT pre-Tisa-cel may prompt consideration of further lines of BT where possible

    Chikungunya Virus and Central Nervous System Infections in Children, India

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    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus best known for causing fever, rash, arthralgia, and occasional neurologic disease. By using real-time reverse transcription–PCR, we detected CHIKV in plasma samples of 8 (14%) of 58 children with suspected central nervous system infection in Bellary, India. CHIKV was also detected in the cerebrospinal fluid of 3 children

    Measuring the capability to raise revenue process and output dimensions and their application to the Zambia revenue authority

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    The worldwide diffusion of the good governance agenda and new public management has triggered a renewed focus on state capability and, more specifically, on the capability to raise revenue in developing countries. However, the analytical tools for a comprehensive understanding of the capability to raise revenue remain underdeveloped. This article aims at filling this gap and presents a model consisting of the three process dimensions ‘information collection and processing’, ‘merit orientation’ and ‘administrative accountability’. ‘Revenue performance’ constitutes the fourth capability dimension which assesses tax administration’s output. This model is applied to the case of the Zambia Revenue Authority. The dimensions prove to be valuable not only for assessing the how much but also the how of collecting taxes. They can be a useful tool for future comparative analyses of tax administrations’ capabilities in developing countries.Die weltweite Verbreitung der Good-Governance- und New-Public-Management-Konzepte hat zu einer zunehmenden Konzentration auf staatliche LeistungsfĂ€higkeit und, im Besonderen, auf die LeistungsfĂ€higkeit der Steuererhebung in EntwicklungslĂ€ndern gefĂŒhrt. Allerdings bleiben die analytischen Werkzeuge fĂŒr ein umfassendes VerstĂ€ndnis von LeistungsfĂ€higkeit unterentwickelt. Dieser Artikel stellt hierfĂŒr ein Modell vor, das die drei Prozess-Dimensionen „Sammeln und Verarbeiten von Informationen“, „Leistungsorientierung der Mitarbeiter“ und „Verantwortlichkeit der Verwaltung“ beinhaltet. „Einnahmeperformanz“ ist die vierte Dimension und erfasst den Output der Steuerverwaltung. Das mehrdimensionale Modell wird fĂŒr die Analyse der LeistungsfĂ€higkeit der Steuerbehörde Zambias (Zambia Revenue Authority) genutzt. Es erweist sich nicht nur fĂŒr die Untersuchung des Wieviel, sondern auch des Wie des Erhebens von Steuern als wertvoll. Die vier Dimensionen können in Zukunft zur umfassenden und vergleichenden Analyse der LeistungsfĂ€higkeit verschiedener Steuerverwaltungen in EntwicklungslĂ€ndern genutzt werden
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